Molecular epidemiology study on carcinogenic mechanism of Epstein-Barr-associated nasopharyngeal carcinoma and modification by environmental factors in southern China

EB病毒感染的鼻咽癌（NPC）是中国南方的一个重要的健康问题。我们从中国南方的鼻咽癌患者中获得血清和鼻咽组织活检标本。我们进行了双重免疫荧光染色，以检查这些标本中硝化和氧化DNA损伤（8-硝基鸟嘌呤和8-氧代-7，8-二氢-2 '-脱氧鸟苷（8-oxodG））的形成。鼻咽癌患者的癌细胞和炎性细胞均出现DNA损伤。癌细胞胞浆内iNOS呈强阳性反应。EGFR的核积聚和IL-6激活STAT 3可能在iNOS表达和由此产生的DNA损伤中起关键作用，导致EBV介导的NPC。鼻咽癌患者血清8-oxodG水平明显高于对照组。在所有6种鼻咽癌细胞系和大部分原发性鼻咽癌组织中均检测到Ras相关糖尿病基因（RRAD）启动子甲基化。这些发现可能为预防NPC的发展提供策略。

Epstein-Barr virus-infected nasopharyngeal carcinoma (NPC) is an important health problem in southern China. We obtained serum and biopsy specimens of nasopharyngeal tissues from NPC patients in southern China. We performed double immunofluorescent staining to examine the formation of nitrative and oxidative DNA lesions (8-nitroguanine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) in these specimens. DNA lesions were observed in cancer cells and inflammatory cells of NPC patients. Intensive immunoreactivity of iNOS was detected in the cytoplasm of cancer cells. Nuclear accumulation of EGFR and STAT3 activation by IL-6 may play the key role in iNOS expression and resultant DNA damage, leading to EBV-mediated NPC. The serum level of 8-oxodG in the NPC patients was significantly higher than that in the control. Promoter hypermethylation of Ras-related associated with diabetes (RRAD) was detected in all six NPC cell lines and most of primary NPC tissues. These findings may provide a strategy for preventing the development of NPC.